The implementation of ICH Q3D has already become in a reality, and the requirements and implementation dates represent a challenge for the pharmaceutical industry. Based on the document ‘Implementation strategy of ICH Q3D guideline’ (EMA/CHMP/QWP/115498/2017 – Committee for Medicinal Products for Human use (CHMP), there are two different approaches to risk management of elemental impurities in drug products: drug product approach and component approach.
The immediate question is: ‘What is the best option for my company?’ The answer is not that straight forward; there are several points to consider! First, it should be noted that, as stated in the previously mentioned document, the use of the component approach is encouraged due to its advantages from a scientific and transparency point of view. However, the drug product approach might be a better option in certain cases (when time is the most critical parameter). A combined strategy can be also considered: start with component approach and, when necessary, cover data gaps by testing elemental impurities in the finished drug product to demonstrate compliance in due time by the product approach.
Resources (analytical equipment, personnel, economic, time) are critical parameters to consider. Without a prior planning and a good optimization of the resources, the overall cost of ICH Q3D implementation can be increased to significant levels.
Therefore, the aim of this document is to describe our experience with representative real examples of our customers, through comparison of the estimated and the actual costs of the implementation of ICH Q3D.
|Company||Portfolio||Estimated cost (€)1||Approach2||Number of analysis required3||Actual Cost (€)4||Project duration (months)||Savings (%)|
|Generic drugs manufacturer||110||275,000||C||18||90,000||12||67,3|
|Multinational innovative MAH||20||50,000||DP||20||45,000||2||10,0|
|Small size manufacturer||6||15,000||C||1||7,500||2||50,0|
|R&D Department (Licensor)||12||30,000||CS||7||18,000||3||40,0|
|Large size CDMO||60||150,000||CS||12||70,000||7||53,3|
|Generics & OTC manufacturer||80||200,000||C||6||70,000||9||65,0|
|Small size OTC manufacturer||15||37,500||CS||5||22,000||3||41,3|
|Large size CMO||100||250,000||C||9||90,000||11||64,0|
|Medium size CDMO||34||85,000||C||0||24,000||7||71,8|
|Medium size CMO||40||100,000||C||7||36,000||7||64,0|
|Manufacturer and MAH||25||62,500||C||2||25,000||6||60,0|
|Large size CDMO||77||192,500||C||3||53,000||12||72,5|
|Manufacturer (MAH) and CMO||40||100,000||C||7||42,000||8||58,0|
|Medium size CMO||35||87,500||CS||11||58,500||6||33,1|
|Parenteral drug manufacturer||40||100,000||C||9||55,000||8||45,0|
|Small size manufacturer/MAH||11||27,500||C||2||16,000||3||41,8|
|Medium size CMO||22||55,000||C||2||28,000||5||49,1|
|MAH (outsourced manufacturing)||14||35,000||CS||9||25,000||3||28,6|
1: Estimation based on the analytical cost and time required for the risk assessment.
2: C: Component; DP: Drug product; CS: Combined strategy.
3: Number of products and/or components that have required experimental testing by customer.
4: Approximate result based on the price of Azierta and the actual analytical costs.
The implementation by the component-approach is the most cost-effective option, with an average saving of 59.4% compared to the estimated cost.
The statistics show that bigger companies (in terms of number of products) can take more advantage from a good planning (average 64.4%).
Small size: Portfolio ≤20 products / Medium size: 20<Portfolio≤50 / Large size: Portfolio > 50 products
The component approach will generally require more time than the product approach. This fact is reflected in the following graph showing the average time (in months) required for finishing the risk assessment of 10 products.
As overall conclusion, the optimization of resources can lead to very important savings while keeping a high-quality standard: A good planning is the key for a successful implementation in a reasonable time with a reasonable cost!
Our experience demonstrates that the component approach is a cost-effective solution for the implementation of ICH Q3D. It provides high-quality risk assessments at a significantly reduced cost.
If you want more information please visit www.azierta.eu
Or contact us by email: firstname.lastname@example.org
Authors: Ignacio Jorge & Paulino Alonso. Azierta